Prevention and treatment of skin infections has been, and continues to be, important. Each year 41,000 central line-associated bloodstream infections (CLABSI) occur within US hospitals (see Centers for Disease Control and Prevention CLABSI Report 2012, incorporated herein by reference). There are two common routes of pathogenic colonization of the bloodstream during catheter use: through the skin defect that was created for the catheter, and/or through the catheter lumen itself. These catheters, generally known as tunneled and non-tunneled central venous lines, are used both for administration of medication or alimentation as well as withdrawal of blood samples for monitoring the patient. See FIG. 1.
Similarly, skin defects created by surgical procedures can also carry a risk of infection. Each year more than 150,000 such infections occur within acute care hospitals. (Magill, S. S., et al., “Multistate point-prevalence survey of health care-associated infections”. New England Journal of Medicine, 370(13): (2014): 1198-208). Bacterial growth in the surgical wound, even in the absence of an overt infection, can slow or inhibit the healing process (Granick, M. S. & Teot, L. Surgical Wound Healing and Management, Second Edition, CRC Press, 2012).
A random sampling of post-surgical wounds demonstrated that 20% of them have at least 100,000 organisms per gram of tissue (Robson, M. C., Duke, W. F., and Krizek, T. J. (1973). Rapid bacterial screening in the treatment of civilian wounds. Journal of Surgical Research 14, 426-430). Furthermore, both types of infections can be prevented to a large extent.
Methods used to reduce catheter related infections can include: 1) impregnation of the catheter with antibacterial agents, such as silver sulfadiazine; 2) placement of chlorhexidine gluconate (CHG) impregnated discs at the level of the catheter-related skin defect (has been shown to reduce infections by as much as 69%); 3) frequent flushing of the catheter with saline solutions; 4) placement of alcohol caps at the luer locks of the catheter; as well as other methods.
Each of these methods can reduce infections, but due to the wide spread use of these catheters both in the acute setting as well as their long term use in areas such as hemodialysis, CLABSI costs thousands of lives and millions of dollars annually. In addition, each of theses methods has drawbacks, not the least of which is cumulative additive costs as well as staff time for their deployment.
Radiation can inhibit the growth of microorganisms through inhibition of normal cellular mechanisms either through direct interaction with DNA or through creation of intermediaries such as oxygen radicals. UV radiation, specifically, is used in numerous fields ranging from water and food treatment to medical equipment sterilization.
The various wavelengths of ultraviolet (UV) light fall in three categories: UVA (near UV) 315-400 nm, UVB (middle UV) 280-315 nm, and UVC (far UV) 180-280 nm.
It is known that UVB and UVC have antibacterial properties. In previous work on the utility of UVB for treatment of water, treatment with 100 J/m2 (or 10 mW/cm2) of UVB resulted in an almost 100 fold reduction of bacterial growth. The dose-response curve obtained was logarithmic (Techneau, Development of UV-LED Disinfection, February 2010, and Hamamoto, A. et al. New water disinfection system using UVA light-emitting diodes. Journal of Applied Microbiology 103, 2291-2298 (2007), incorporated herein by reference in its entirety).
UVB and UVC hence have been utilized in the above fields because they directly damage DNA of organisms but UVA, despite its better penetration profile, has not been used as a sole option for the inhibition of microorganism growth. In comparison to UVB and UVC, UVA is characterized by a longer wavelength with better penetration profile. There is significant loss of the shorter wavelengths even in normal oils or at most the top epidermis skin layer (Ultraviolet Radiation Guide. (1992) found online at <http://www.med.navy.mil/sites/nmcphc/Documents/policy-and-instruction/ih-ultraviolet-radiation-technical-guide.pdf> Ultraviolet Radiation Guide, incorporated herein by reference). It has been generally agreed upon that UVA is not, by itself, effective in controlling bacterial populations (Ye, L., Martinez, S. G., Swain, L., Zhao, Z. & Moller, K. Disinfection Using UVA Light on Glass Surfaces with or without Titanium Dioxide Coating. in (iCBBE) 2011 5th International Conference on Bioinformatics and Biomedical Engineering 1-3 (2011). doi:10.1109/icbbe.2011.5780340, incorporated herein by reference). UVA is not well absorbed by DNA but it can produce free radicals which can damage multiple pathways important for maintenance of biological function of microorganisms. Table 1 (Ye, L., Martinez, S. G., Swain, L., Zhao, Z., and Moller, K. (2011). Disinfection Using UVA Light on Glass Surfaces with or without Titanium Dioxide Coating. In (iCBBE) 2011 5th International Conference on Bioinformatics and Biomedical Engineering, pp. 1-3) illustrates how combined utilization of Titanium Oxide and UVA significantly reduced bacterial growth. The control column illustrates that there was a significant drop in S. aureus and E. faecium as well as the fungus Candida, a common human fungal infection.
TABLE 1Inactivation of various bacteria by photocatalysis on TiO2-coated Plexiglas ® with UVA light (60 min)Initial germFinal germControl final germMulti-count ± errorcount ± errorcount ± errorReductionGermplicity(CFU/ml)(CE in CFU/ml)(CCE in CFU/ml)efficiencyE. coli31.2 × 107 ± 0.09 × 107<5—1.1 × 107 ± 0.13 × 107>6.3P. aeruginosa41.5 × 106 ± 0.12 × 106<5—1.2 × 106 ± 0.22 × 106>5.4S. aureus20.8 × 105 ± 0.15 × 105<5—4.3 × 106 ± 2.6 × 104 >3.9E. faecium43.6 × 107 ± 0.36 × 1071.3 × 1022.5 × 1041.6 × 107 ± 0.51 × 1073.1C. albicans31.1 × 105 ± 0.08 × 1054.1 × 1036.2 × 1036.2 × 106 ± 1.1 × 104 1.2Reduction efficiencies (RE) = log10 (CCE − CE); CE = number of viable cells in CFU/ml after irradiation; CCE = number of viable cells of the control in CFU/ml after irradiation; error: at multiplicity n ≥ 3; standard deviation of the mean; at n < 3: error = ½ × (value 1 − value 2).